tert-butyl[(5-fluoro-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[1,3]dioxol-4-yl)oxy]diphenylsilane | 663190-26-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: tert-butyl[(5-fluoro-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[1,3]dioxol-4-yl)oxy]diphenylsilane
• 英文别名: tert-butyl ((3aR,4R,6aR)-5-fluoro-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yloxy)diphenylsilane；Tert-butyl((3aR,4R,6aR)-5-fluoro-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yloxy)diphenylsilane；[(3aR,4R,6aR)-5-fluoro-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]oxy-tert-butyl-diphenylsilane
• CAS: 663190-26-9
• 化学式: C₂₄H₂₉FO₃Si
• 分子量: 412.576
• InChiKey: NDZSPQOLNHZBAO-BHIFYINESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.32
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  27.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl[(5-fluoro-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[1,3]dioxol-4-yl)oxy]diphenylsilane 在 四丁基氟化铵 、 水 作用下， 以 四氢呋喃 、 乙酸乙酯 为溶剂， 反应 2.0h， 生成 (3AS,4R,6AR)-5-氟代-2,2-二甲基-3A,6A-二氢-4H-环戊二烯[D][1,3]二氧六环-4-醇
  参考文献：
  名称：

  AHCY HYDROLASE INHIBITORS FOR TREATMENT OF HYPER HOMOCYSTEINEMIA

  摘要：

  本发明涉及式(I)的AHCY抑制剂，对于治疗高同型半胱氨酸水平疾病（如阿尔茨海默病）具有益处。该发明还涉及包含这些化合物的药物组合物，以及在治疗高同型半胱氨酸水平疾病中使用这些化合物和组合物。

  公开号：

  US20110160229A1
• 作为产物：
  描述：

  (3AS,4S,6AR)-2,2-二甲基-3A,6A-二氢-4H-环戊[D][1,3]二噁酚-4-醇 在 吡啶 、 咪唑 、 sodium tetrahydroborate 、 正丁基锂 、 cerium(III) chloride 、 碘 、 N-氟代双苯磺酰胺 作用下， 以 四氢呋喃 、 甲醇 、 hexanes 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 73.75h， 生成 tert-butyl[(5-fluoro-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[1,3]dioxol-4-yl)oxy]diphenylsilane
  参考文献：
  名称：

  AHCY HYDROLASE INHIBITORS FOR TREATMENT OF HYPER HOMOCYSTEINEMIA

  摘要：

  本发明涉及式(I)的AHCY抑制剂，对于治疗高同型半胱氨酸水平疾病（如阿尔茨海默病）具有益处。该发明还涉及包含这些化合物的药物组合物，以及在治疗高同型半胱氨酸水平疾病中使用这些化合物和组合物。

  公开号：

  US20110160229A1

文献信息

• AHCY hydrolase inhibitors for treatment of hyper homocysteinemia
  申请人：Converso Antonella

  公开号：US08629275B2

  公开（公告）日：2014-01-14

  The present invention is directed to AHCY inhibitors of formula (I): which are useful in the treatment of diseases characterized by high homocysteine levels, such as Alzheimer's disease. The invention is also directed to pharmaceutical compositions comprising the compounds, and to the use of the compounds and compositions in the treatment of diseases characterized by high homocysteine levels.

  本发明涉及公式(I)的AHCY抑制剂，其可用于治疗高同型半胱氨酸水平的疾病，如阿尔茨海默病。本发明还涉及包含该化合物的制药组合物，以及在治疗高同型半胱氨酸水平的疾病中使用该化合物和组合物的方法。
• X-ray Crystal Structure and Binding Mode Analysis of Human <i>S</i>-Adenosylhomocysteine Hydrolase Complexed with Novel Mechanism-Based Inhibitors, Haloneplanocin A Analogues
  作者：Kang Man Lee、Won Jun Choi、Yoonji Lee、Hyun Joo Lee、Long Xuan Zhao、Hyuk Woo Lee、Jae Gyu Park、Hea Ok Kim、Kwang Yeon Hwang、Yong-Seok Heo、Sun Choi、Lak Shin Jeong

  DOI：10.1021/jm1010836

  日期：2011.2.24

  The X-ray crystal structure of human S-adenosylhomocysteine (AdoHcy) hydrolase was first determined as a tetrameric form bound with the novel mechanism-based inhibitor fluoroneplanocin A (4b). The crystallized enzyme complex showed the closed conformation and turned out to be the intermediate of mechanism-based inhibition. It confirmed that the cofactor depletion by 3'-oxidation of fluoroneplanocin A contributes to the enzyme inhibition along with the irreversible covalent modification of AdoHcy hydrolase. In addition, a series of haloneplanocin A analogues (4b-e and 5b-e) were designed and synthesized to characterize the binding role and reactivity of the halogen substituents and the 4'-CH2OH group. The biological evaluation and molecular modeling studies identified the key pharmacophores and structural requirements for the inhibitor binding of AdoHcy hydrolase. The inhibitory activity was decreased as the size of the halogen atom increased and/or if the 4'-CH2OH group was absent. These results could be utilized to design new therapeutic agents operating via AdoHcy hydrolase inhibition.
• Synthesis of Halogenated 9-(Dihydroxycyclopent-4′-enyl) Adenines and Their Inhibitory Activities Against<i>S</i>-Adenosylhomocysteine Hydrolase
  作者：Lak Shin Jeong、Jae Gyu Park、Won Jun Choi、Hyung Ryong Moon、Kang Man Lee、Hea Ok Kim、Hee-Doo Kim、Moon Woo Chun、Hea-Young Park、Kilhyoun Kim、Yhun Y. Sheen

  DOI：10.1081/ncn-120022686

  日期：2003.10

  Novel halovinyl analogues of neplanocin A without 4'-hydroxymethyl group were easily synthesized starting from D-ribose via cyclopentenone 5 as a key intermediate and their inhibitory activity against SAH hydrolase was assayed.
• Truncated Fluorocyclopentenyl Pyrimidines as <i>S</i>-Adenosylhomocysteine Hydrolase Inhibitors
  作者：Yeon Hee Park、Won Jun Choi、Amol S. Tipnis、Kang Man Lee、Lak Shin Jeong

  DOI：10.1080/15257770903054316

  日期：2009.8.11

  On the basis of inhibitory activity of truncated cyclopentenyl cytosine against S-adenosylhomocysteine hydrolase (SAH), its fluorocyclopentenyl Pyrimidine derivatives were efficiently synthesized from D-ribose via electrophilic fluorination as a key step. The final nucleosides were evaluated for SAH inhibitory activity, among which the uracil derivative 9 showed significant inhibitory activity (IC50 = 8.53 mu M). They were also evaluated for cytotoxic effects in several human cancer cell lines such as fibro sarcoma, stomach cancer, Leukemia, and colon cancer, but they did not show any cytotoxic effects up to 100 mu M, indicating that 4'-hydroxymethyl groups are essential for the anticancer activity.